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NCT04334317

A Study of TAK-071 in People With Parkinson Disease

Completed Phase 2 Results posted Last updated 14 May 2024
What this trial tests

Phase 2 trial testing TAK-071 in Parkinson Disease in 64 participants. Completed in 27 February 2023.

Timeline
21 October 2020
Primary endpoint
27 February 2023
27 February 2023

Quick facts

Lead sponsorTakeda
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingquadruple
Primary purposetreatment
Enrollment64
Start date21 October 2020
Primary completion27 February 2023
Estimated completion27 February 2023
Sites21 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 40 to 85, any sex, with Parkinson Disease or Healthy Participants. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Main Cohort: Change From Baseline in Stride Time (Gait) Variability During a 2-minute Dual-Task Walking Test After 6-week Treatment With TAK-071 Compared With Placebo Primary · Baseline and Week 6 (for each study period)

Stride time (or gait) is defined as the time elapsed between the first contact of two consecutive footsteps of the same foot and is expressed in seconds. The standard deviation (SD) of the stride time, recorded for each foot during the 2-minutes, is averaged to obtain stride time (gait) variability. The 2-minute walk was performed with and without simultaneous performance of serial 3 subtraction, which adds a cognitive load to the task. Data are reported with and without cognitive load.

Baseline
GroupValue95% CI
Without Cognitive Load: Placebo0.0546± 0.03919
Without Cognitive Load: TAK-0710.0625± 0.05601
With Cognitive Load: Placebo0.0930± 0.07743
With Cognitive Load: TAK-0710.0861± 0.06047
Week 6
GroupValue95% CI
Without Cognitive Load: Placebo0.0534± 0.03638
Without Cognitive Load: TAK-0710.0607± 0.05666
With Cognitive Load: Placebo0.0848± 0.07894
With Cognitive Load: TAK-0710.0925± 0.08156
Sentinel Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-071 in Healthy Participants Primary · Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
GroupValue95% CI
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)186± 35.0
Sentinel Cohort, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-071 in Healthy Participants Primary · Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
GroupValue95% CI
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)1.501.00 – 8.00
Sentinel Cohort, AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for TAK-071 in Healthy Participants Primary · Day 1: Predose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post dose
GroupValue95% CI
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)3050± 20.7
Sentinel Cohort, AUClast: Area Under The Concentration-Time Curve From Time 0 To The Last Quantifiable Concentration in Healthy Participants Primary · Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
GroupValue95% CI
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)11800± 19.2
Sentinel Cohort, AUCinf: Area Under The Concentration-Time Curve From Time 0 To Infinity in Healthy Participants Primary · Day 1: pre-dose and Day 2 to 8: post-dose and at multiple time-points (up to approximately 168 hours)
GroupValue95% CI
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)14600± 28.7
Main Cohort: Change From Baseline in Global Cognition Z-score Secondary · Baseline and Week 6 (for each study period)

The global cognition score was calculated as the average of the available z-scores derived from the following individual cognitive tests administered in the cognitive test battery: 'Executive Function' assessed by One Back Test, Modified Groton Maze Learning Test, 'Memory' assessed by One Card Learning Test, International Shopping List Test - Immediate and Delayed Recall Tests, and 'Attention' assessed by Sustained Attention Test and Symbol Digit Modalities Test. Each raw score on the individual tests was converted to a z-score. A global z-score was calculated as an average of the individual z

GroupValue95% CI
Placebo-0.059± 0.3671
TAK-0710.208± 0.3940
Main Cohort: Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-071 in Parkinson Disease (PD) Participants Secondary · Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
GroupValue95% CI
TAK-071339± 43.7
Main Cohort, Cmax: Maximum Observed Plasma Concentration for TAK-071 in PD Participants Secondary · Day 1 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
GroupValue95% CI
TAK-071125± 33.4
Main Cohort: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for TAK-071 in PD Participants Secondary · Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
GroupValue95% CI
TAK-071480± 34.4
Main Cohort: AUC24: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours for TAK-071 in PD Participants Secondary · Day 1 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
GroupValue95% CI
TAK-0712360± 32.6
Main Cohort, AUCtau: Area Under the Plasma Concentration-time Curve During a Dosing Interval for TAK-071 in PD Participants Secondary · Day 42 of Period 1 and Period 2: pre-dose and at multiple time-points post-dose
GroupValue95% CI
TAK-0719360± 38.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From signing of the informed consent form up to 22 days after the last dose of study treatment (up to approximately 148 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Main Cohort: Placebo (PD Participants)
Serious: 1/49 (2%)
Deaths: 0/49
Main Cohort: TAK-071 (PD Participants)
Serious: 2/53 (4%)
Deaths: 0/53
Sentinel Cohort: Placebo (Healthy Participants)
Serious: 0/2 (0%)
Deaths: 0/2
Sentinel Cohort: TAK-071 7.5 mg (Healthy Participants)
Serious: 0/8 (0%)
Deaths: 0/8

Serious adverse events (1 terms)

ReactionSystemMain Cohort: Placebo (PD P…Main Cohort: TAK-071 (PD P…Sentinel Cohort: Placebo (…Sentinel Cohort: TAK-071 7…
COVID-19Infections and infestations
Other adverse events (6 terms — click to expand)

ReactionSystemMain Cohort: Placebo (PD P…Main Cohort: TAK-071 (PD P…Sentinel Cohort: Placebo (…Sentinel Cohort: TAK-071 7…
DizzinessNervous system disorders
HeadacheNervous system disorders
Blood creatine phosphokinase increasedInvestigations
Loss of consciousnessNervous system disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Road traffic accidentInjury, poisoning and procedural complications

Most-reported serious reactions: COVID-19.

Data from ClinicalTrials.gov NCT04334317 adverse events section.

Sponsor's own description

It is hoped that TAK-071 will help people with Parkinson's disease to walk with better balance. The main aim of the study is to check if there is a difference in how participants walk after treatment with TAK-071. Another aim is to see if it improves how participants think and remember. At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 groups by chance. Both groups will have 2 treatments but in a different order. The treatments are TAK-071 tablets or placebo. In this study, a placebo will look like the TAK-071 but will not have any medicine in it. One group will take TAK-071 for 6 weeks, have at least a 3-week break, then take a placebo for 6 weeks. The other group will take a placebo for 6 weeks, have at least a 3-week break, then take TAK-071 for 6 weeks. The participants will not know the order of their 2 treatments, nor will their study doctors. This is to help make sure the results are more reliable. The participants will visit the clinic at the beginning and end of each treatment for a check-up. 14 days after the 2nd treatment, clinic staff will telephone the participants for a final check-up.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.
    Xie X, Yu T, Li X, Zhang N, et al · · 2023 · cited 246× · PMID 37669923 · DOI 10.1038/s41392-023-01589-z
  2. Alzheimer's and Parkinson's disease therapies in the clinic.
    Chopade P, Chopade N, Zhao Z, Mitragotri S, et al · · 2023 · cited 96× · PMID 36684083 · DOI 10.1002/btm2.10367
  3. Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.
    Johnson CR, Kangas BD, Jutkiewicz EM, Bergman J, et al · · 2022 · cited 34× · PMID 35203607 · DOI 10.3390/biomedicines10020398
  4. Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease.
    Di Luca DG, Reyes NGD, Fox SH. · · 2022 · cited 21× · PMID 35841520 · DOI 10.1007/s40265-022-01747-7
  5. Parkinson's disease therapy: what lies ahead?
    Wolff A, Schumacher NU, Pürner D, Machetanz G, et al · · 2023 · cited 19× · PMID 37147404 · DOI 10.1007/s00702-023-02641-6
  6. An Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial.
    Shanbhag NM, Padmanabhan JL, Zhang Z, Harel BT, et al · · 2025 · cited 10× · PMID 39761063 · DOI 10.1001/jamaneurol.2024.4519
  7. Muscarinic control of cardiovascular function in humans: a review of current clinical evidence.
    Palma JA. · · 2024 · cited 9× · PMID 38305989 · DOI 10.1007/s10286-024-01016-5
  8. Population Pharmacokinetic and Exposure-Response Analysis of the Cognitive Effects of TAK-071 in Participants With Parkinson Disease and Cognitive Impairment.
    Jia H, Facius A, Jennings R, Hang Y, et al · · 2025 · PMID 40711392 · DOI 10.1002/cpdd.1579

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing